Pregledni rad
EXTRAGLYCEMIC EFFECTS OF LIRAGLUTIDE, HUMAN GLUCAGON-LIKE PEPTIDE-1 ANALOG
TOMISLAV BULUM
orcid.org/0000-0003-4808-2968
; Klinička bolnica Merkur, Sveučilišna klinika za dijabetes, endokrinologiju i bolesti metabolizma Vuk Vrhovac i Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, Hrvatska
LEA DUVNJAK
; Klinička bolnica Merkur, Sveučilišna klinika za dijabetes, endokrinologiju i bolesti metabolizma Vuk Vrhovac i Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, Hrvatska
Sažetak
Glucagon-like peptide-1 (GLP-1) is a gut hormone that stimulates insulin secretion in a glucose-dependent manner. The GLP-1 analog liraglutide has 97% homology to native GLP-1, and across the six LEAD (Liraglutide Effect and Action in Diabetes) trials, liraglutide improved hemoglobin A1c and was associated with sustained body weight with a low risk of hypoglycemia in different type 2 diabetes populations. However, trial data suggest that GLP-1 receptor agonists have effects
beyond their glycemic actions because GLP-1 receptors are widely expressed in extra-pancreatic tissues such as heart (including endothelium and cardiac and vascular myocytes), gastrointestinal tract, liver, kidney, and peripheral and central nervous systems. Type 2 diabetes is commonly associated with hypertension, dyslipidemia, obesity and nephropathy, and cardiovascular disease is a major cause of mortality. GLP-1 receptor agonists represent signifi cant advance in the treatment of type 2 diabetes because they uniquely affect a broad array of cardiovascular risk factors through signifi cant weight, systolic blood pressure, serum lipids and albuminuria reduction. Studies support a cardioprotective role of liraglutide on vascular endothelium and myocardium, including vasodilatation and anti-infl ammatory effects. Treatment with liraglutide was associated with reductions in total cholesterol, LDL-cholesterol and triglycerides. Treatment with
liraglutide reduces systolic blood pressure via effects on renal sodium excretion and peripheral vasodilatation. Liraglutide signifi cantly reduces hepatic lipogenesis, hepatic and adipose insulin resistance, and adipose infl ammation in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Activation of GLP-1 receptor has a crucial role in the protection against increased renal oxidative stress under chronic hyperglycemia, and treatment with liraglutide reduces albuminuria, attenuates mesangial expansion, enhances nitric oxide levels and improves glomerular fi ltration. GLP-1 receptor agonists have also been shown to exert a neuroprotective role in animal models of Alzheimer’s disease and Parkinson’s disease. Long-term, prospective, randomized LEADER study (the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) with large patient populations demonstrated that persons with type 2 diabetes who were at a high risk of cardiovascular events had lower rates of cardiovascular events with liraglutide than with placebo.
Ključne riječi
glucagon-like peptide -1 receptor agonist; type 2 diabetes; liraglutide; cardiovascular risk
Hrčak ID:
186103
URI
Datum izdavanja:
2.9.2017.
Posjeta: 2.845 *